Intra-operative confocal imaging to guide Mohs surgery

术中共聚焦成像指导莫氏手术

• 批准号: 8146034
• 负责人: MILIND RAJADHYAKSHA
• 金额: $ 78.53万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-30 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8146034
• 关键词: Aluminum; Anesthesia procedures; Area; Atlas of Cancer Mortality in the United States; Basal cell carcinoma; Biopsy; Bladder; Breast; Cellular Morphology; Cervical; Chloride Ion; Chlorides; Clinical; Clinical Research; Confocal Microscopy; Contrast Media; Dermatology; Detection; Development; Diagnosis; Epidermis; Excision; Face; Freezing; Funding; Funding Opportunities; Future; Goals; Gold; Head and neck structure; Healthcare; Human; Image; In Situ; Incidence; Laboratories; Lateral; Left; Liver; Malignant Neoplasms; Maps; Microscope; Mohs Surgery; Morphology; Motivation; National Institute of Biomedical Imaging and Bioengineering; Normal tissue morphology; Nuclear; Operating Rooms; Operative Surgical Procedures; Optics; Oral; Pain; Pathology; Patients; Preparation; Procedures; Resolution; Scanning; Screening procedure; Sensitivity and Specificity; Shave Biopsy; Skin; Skin Cancer; Squamous cell carcinoma; Staining method; Stains; Surgical wound; Technology; Testing; Time; Tissues; Topical application; Translating; base; cancer type; cost; image guided intervention; in vivo; instrument; instrumentation; interest; intervention program; melanoma; public health relevance; response

DESCRIPTION (provided by applicant): The goal of this project is to translate a bench-top line-scanning confocal microscope into a clinical instrument for intra-operative imaging during Mohs surgery, and to test feasibility for detecting basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) margins on patients, using aluminum chloride as a contrast agent for staining nuclear morphology in reflectance. Reaching clinically expected sensitivity and specificity will be the quantitative milestones to validate and demonstrate a technology platform for Mohs surgery in skin and other potentially diverse intra-operative imaging applications. The motivation is to create a relatively simple, small and low-cost confocal microscope for real-time imaging in reflectance, to guide surgery in diverse settings. The proposed immediate application is intra-operative mapping of BCCs and SCCs to guide Mohs surgery. Future applications may include mapping of cancers to guide surgery in oral, head-and-neck, breast, bladder, liver and other tissues. BCCs and SCCs occur with among the highest rates of incidence, with an estimated 1.3 million new cases diagnosed and an estimated 1 million surgeries performed every year in the USA alone. Surgery is guided by frozen pathology which is labor-intensive and time-consuming. Confocal microscopy images nuclear detail in vivo and thus may enable intra-operative mapping directly on the patient in real-time. Rapid examination of cancer margins may be performed on surgically exposed tissue in situ, to guide accurate and complete excision, while preserving surrounding normal tissue. The imaging may serve as an adjunct to pathology for guiding surgery, while saving labor and cost. Patients may benefit with more efficient procedures, less anesthesia and less time in the operating room. Preliminary results demonstrate the feasibility of detecting BCCs, with topically applied aluminum chloride to enhance cancer-to-normal tissue contrast, in surgically-exposed shave-biopsy wounds in situ on patients. Furthermore, a laboratory bench-top line-scanning confocal microscope demonstrates excellent imaging of nuclear and cellular detail in human skin in vivo. The optical sectioning is 1.7 ¿m and lateral resolution is 0.8 ¿m, which is comparable to that of pathology. The hardware cost of the bench-top microscope is less than $15,000. Our hypothesis is that the bench-top line-scanning instrumentation may be translated toward a compact confocal microscope for use at-the-bedside. Rapid and safe staining of nuclear morphology with aluminum chloride may enable intra-operative mapping, in reflectance contrast, of BCCs and SCCs to guide surgery. The specific aims are (1) to build a compact line-scanning confocal microscope for intra-operative imaging in reflectance contrast, and (b) to test the microscope and aluminum chloride-based contrast for intra operative detection of BCC and SCC margins in surgical wounds in situ during Mohs surgery, in a pilot clinical study on 60 patients. Sensitivity and specificity will be determined, against the gold standard of Mohs frozen pathology, to validate the feasibility of the technology. PUBLIC HEALTH RELEVANCE: Confocal microscopy may enable screening and diagnosis of skin cancers such as melanomas and basal- and squamous-cell carcinomas, or may guide surgery of such cancers, directly and in real-time on the patient. The screening, diagnosis or surgical guidance may be noninvasive, with minimal need for biopsy, minimal pain and minimal expense. In dermatology alone, US healthcare may potentially save $2 billion every year. Confocal microscopy may also prove useful for noninvasively diagnosing and treating many other types of cancers such as oral, head-and-neck, breast and cervical.

描述（由申请人提供）：本项目的目标是将台式线扫描共聚焦显微镜转化为莫氏手术期间术中成像的临床仪器，并测试使用氯化铝作为对比剂对反射率中的核形态进行染色以检测患者基底细胞癌（BCC）和鳞状细胞癌（SCC）边缘的可行性。达到临床预期的灵敏度和特异性将是量化的里程碑，以验证和证明皮肤莫氏手术和其他潜在的不同术中成像应用的技术平台。其动机是创建一个相对简单，小型和低成本的共焦显微镜，用于实时成像的反射，以指导手术在不同的设置。建议的直接应用是术中绘制BCC和SCC，以指导Mohs手术。未来的应用可能包括绘制癌症地图，以指导口腔、头颈部、乳腺、膀胱、肝脏和其他组织的手术。BCC和SCC的发病率最高，仅在美国每年就有估计130万例新诊断病例和估计100万例手术。手术由冷冻病理学指导，这是劳动密集型和耗时的。共聚焦显微镜成像核细节在体内，因此可以使术中映射直接在病人的实时。可以在原位对手术暴露的组织进行癌边缘的快速检查，以指导准确和完整的切除，同时保留周围的正常组织。成像可以作为病理学的辅助手段，用于指导手术，同时节省劳动力和成本。患者可能会受益于更有效的程序，更少的麻醉和更少的时间在手术室。初步结果表明，局部应用氯化铝，以提高癌症与正常组织的对比度，在患者的原位暴露剃毛活检伤口检测BCC的可行性。此外，实验室台式线扫描共聚焦显微镜展示了人体皮肤细胞核和细胞细节的出色成像。光学切片为1.7 μ m，横向分辨率为0.8 μ m，与病理切片相当。台式显微镜的硬件成本不到15，000美元。我们的假设是，台式线扫描仪器可以被翻译成一个紧凑的共焦显微镜在床边使用。快速和安全的核形态学染色与氯化铝可以使术中映射，在反射率对比度，BCC和SCC，以指导手术。具体目标是：（1）建立一种紧凑型线扫描共聚焦显微镜，用于反射对比度的术中成像，以及（B）在对60名患者进行的初步临床研究中，测试显微镜和基于氯化铝的对比度，用于莫氏手术期间原位手术伤口中BCC和SCC边缘的术中检测。将根据莫氏冷冻病理学的金标准确定灵敏度和特异性，以验证该技术的可行性。 公共卫生关系：共聚焦显微镜可以使得能够筛查和诊断皮肤癌，例如黑色素瘤和基底细胞癌和鳞状细胞癌，或者可以直接地和实时地指导对患者进行这种癌症的手术。筛查、诊断或手术指导可以是非侵入性的，对活检的需求最小，疼痛最小，费用最低。仅在皮肤科，美国医疗保健每年就可能节省20亿美元。共聚焦显微镜也可用于非侵入性诊断和治疗许多其他类型的癌症，如口腔癌、头颈癌、乳腺癌和宫颈癌。